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Research ArticleMetabolism, Transport, and Pharmacogenomics

Experimental evidence for re-secretion of PGE2 across rat alveolar epithelium by OATP2A1/SLCO2A1-mediated transcellular transport

Takeo Nakanishi, Hiroki Takashima, Yuka Uetoko, Hisakazu Komori and Ikumi Tamai
Journal of Pharmacology and Experimental Therapeutics November 12, 2018, jpet.118.249789; DOI: https://doi.org/10.1124/jpet.118.249789
Takeo Nakanishi
Kanazawa University
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Hiroki Takashima
Kanazawa University
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Yuka Uetoko
Kanazawa University
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Hisakazu Komori
Kanazawa University
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Ikumi Tamai
Kanazawa University
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Abstract

Prostaglandin transporter Oatp2a1/Slco2a1 is expressed at the apical (AP) membranes of type-1 alveolar epithelial (AT1) cells. To investigate the role of OATP2A1 in PGE2 handling by alveolar epithelium, we studied PGE2 transport across and secretion from monolayers of rat AT1-like (AT1-L) cells obtained by trans-differentiation of type-2 alveolar epithelial cells (AT2) isolated from male Wistar rats. Rat AT1-L cells expressed Oatp2a1/Slco2a1, together with smaller amounts of Mrp4/Abcc4 and Oct1/Slc22a1. PGE2 uptake was saturable with Km 43.9 ± 21.9 nM. Transcellular transport of PGE2 across AT1-L cells grown on permeable filters in the AP-to-basolateral (BL) direction was 5-fold greater than that in the reverse direction, and was saturable with Km 118 ± 26.8 nM; it was significantly inhibited by OATP inhibitors, bromosulfophthalein (BSP) and suramin, and an MRP4 inhibitor, ceefourin-1. The effects of BSP on the distribution of PGE2 produced by bradykinin-treated AT1-L cells and PGE2-d4 externally added on the AP side of the cells were simultaneously monitored. In the presence of BSP, PGE2 increased more rapidly on the AP side, while PGE2-d4 decreased more slowly on the AP side. The decrease in PGE2-d4 from the AP side corresponded well to the increase on the BL side, indicating that intracellular metabolism did not occur. These results suggest that Oatp2a1 and Mrp4 mediate transepithelial transport of PGE2 in the AP-to-BL direction. Therefore, OATP2A1 may be an important regulator of PGE2 in alveolar epithelium by reducing secretion of PGE2 and facilitating "re-secreting" PGE2 present in the alveolar lumen to the interstitial space or blood.

  • inflammation
  • lipid signaling
  • lung inflammation
  • organic anion
  • organic anion transport
  • prostaglandins
  • prostanoid
  • transporters
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 385 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 385, Issue 3
1 Jun 2023
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Research ArticleMetabolism, Transport, and Pharmacogenomics

Experimental evidence for re-secretion of PGE2 across rat alveolar epithelium by OATP2A1/SLCO2A1-mediated transcellular transport

Takeo Nakanishi, Hiroki Takashima, Yuka Uetoko, Hisakazu Komori and Ikumi Tamai
Journal of Pharmacology and Experimental Therapeutics November 12, 2018, jpet.118.249789; DOI: https://doi.org/10.1124/jpet.118.249789

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Research ArticleMetabolism, Transport, and Pharmacogenomics

Experimental evidence for re-secretion of PGE2 across rat alveolar epithelium by OATP2A1/SLCO2A1-mediated transcellular transport

Takeo Nakanishi, Hiroki Takashima, Yuka Uetoko, Hisakazu Komori and Ikumi Tamai
Journal of Pharmacology and Experimental Therapeutics November 12, 2018, jpet.118.249789; DOI: https://doi.org/10.1124/jpet.118.249789
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